Amino acid chelates for delivery of minerals to biological tissues are described in U.S. Pat. No. 4,863,898. Amino acid chelates in this context refers to the product resulting from the reaction of a polypeptide, dipeptide or naturally occurring alpha amino acid with a metal ion having a valence of two or more to form a ring structure in which the positive electrical charges of the metal ion are neutralized by the electrons available through the carboxylate or free amino groups of the alpha amino acid. As described by U.S. Pat. No. 4,863,898, chelate formation through neutralization of the positive charges of the divalent metal ions can be through the formation of ionic, covalent or coordinate covalent bonding. U.S. Pat. No. 4,863,898 states that it provides an advantage over the prior art metal chelates, which are effective to increase metal content in biological tissues generally, by providing metal chelates targeted to specific tissues. Manganese, calcium, iron, magnesium, copper, and zinc amino acid chelates are among those described.
Polyunsaturated fatty acids of the omega-3 series (“omega-3 fatty acids”) have shown a wide spectrum of biological activities suggesting their possible usefulness in treating a range of diseases and disorders including metabolic disorders, cardiovascular complications, inflammatory diseases, central nervous system disorders, and ophthalmic complications. But the poor aqueous solubility of omega-3 fatty acids limits their utility as therapeutic agents and as nutraceutical additives to food and drink due to a phenomenon referred to as solubility-limited absorption which limits the plasma levels that can be achieved following oral administration. In fact, the omega-3 fatty acids are essentially insoluble in water and both the free acid and sodium salt forms create soap-like emulsions when mixed with water. Thus, although omega-3 fatty acids are absorbed following oral administration, the relatively low plasma levels achieved cannot be increased simply by increasing the dose administered.
WO 2014/011895 describes fatty acid salts of eicosapentaenoic acid (EPA) with lysine or docosahexaenoic acid (DHA) or EPA with metformin, piperazine, and meglumine.
In addition to their poor aqueous solubility, omega-3 fatty acids suffer from susceptibility to lipid oxidation. This oxidation leads to formation of undesirable fishy and rancid off-flavors that render compositions comprising them less palatable.
There is a need to develop compositions able to deliver omega-3 fatty acids at much higher plasma levels than is possible using the currently available free fatty acid, sodium salt, or ester forms, in order to fulfill the therapeutic promise of these compounds and translate the many promising in vitro and cellular pharmacology observations into clinical benefits. Such compositions should demonstrate increased aqueous solubility of omega-3 fatty acids which would facilitate their use in both oral dosage forms, ophthalmic drops, and intravenous dosage forms. There is also a need to develop compositions that provide improved stability of the omega-3 fatty acids against lipid oxidation. The present invention addresses these needs.